Pedro Rada

Bio: Pedro Rada is an academic researcher from University of Los Andes. The author has contributed to research in topics: Nucleus accumbens & Microdialysis. The author has an hindex of 47, co-authored 98 publications receiving 7861 citations. Previous affiliations of Pedro Rada include Princeton University & University of the Andes.

Evidence That Intermittent, Excessive Sugar Intake Causes Endogenous Opioid Dependence

Abstract: COLANTUONI, CARLO, PEDRO RADA, JOSEPH Mc-CARTHY, CAROLINE PATTEN, NICOLE M. AVENA,ANDREW CHADEAYNE, AND BARTLEY G. HOEBEL.Evidence that intermittent, excessive sugar intake causesendogenous opiod dependence. Obes Res. 2002;10:478–488.Objective: The goal was to determine whether withdrawalfrom sugar can cause signs of opioid dependence. Becausepalatable food stimulates neural systems that are implicatedin drug addiction, it was hypothesized that intermittent,excessive sugar intake might create dependency, as indi-cated by withdrawal signs.Research Methods and Procedures: Male rats were food-deprived for 12 hours daily, including 4 hours in the earlydark, and then offered highly palatable 25% glucose inaddition to chow for the next 12 hours. Withdrawal wasinduced by naloxone or food deprivation. Withdrawal signswere measured by observation, ultrasonic recordings, ele-vated plus maze tests, and in vivo microdialysis.Results: Naloxone (20 mg/kg intraperitoneally) causedsomatic signs, such as teeth chattering, forepaw tremor,and head shakes. Food deprivation for 24 hours causedspontaneous withdrawal signs, such as teeth chattering.Naloxone (3 mg/kg subcutaneously) caused reduced timeon the exposed arm of an elevated plus maze, whereagain significant teeth chattering was recorded. The plusmaze anxiety effect was replicated with four controlgroups for comparison. Accumbens microdialysis re-vealed that naloxone (10 and 20 mg/kg intraperitoneally)decreased extracellular dopamine (DA), while dose-depen-dently increasing acetylcholine (ACh). The naloxone-inducedDA/ACh imbalance was replicated with 10% sucrose and 3mg/kg naloxone subcutaneously.Discussion: Repeated, excessive intake of sugar created astate in which an opioid antagonist caused behavioral andneurochemical signs of opioid withdrawal. The indices ofanxiety and DA/ACh imbalance were qualitatively similarto withdrawal from morphine or nicotine, suggesting thatthe rats had become sugar-dependent.Key words: glucose, addiction, dopamine, plus maze,acetylcholine

Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain

Abstract: Palatable food stimulates neural systems implicated in drug dependence; thus sugar might have effects like a drug of abuse. Rats were given 25% glucose solution with chow for 12 h followed by 12 h of food deprivation each day. They doubled their glucose intake in 10 days and developed a pattern of excessive intake in the first hour of daily access. After 30 days, receptor binding was compared to chow-fed controls. Dopamine D-1 receptor binding increased significantly in the accumbens core and shell. In contrast, D-2 binding decreased in the dorsal striatum. Binding to dopamine transporter increased in the midbrain. Opioid mu-1 receptor binding increased significantly in the cingulate cortex, hippocampus, locus coeruleus and accumbens shell. Thus, intermittent, excessive sugar intake sensitized D-1 and mu-1 receptors much like some drugs of abuse.

Sugar and Fat Bingeing Have Notable Differences in Addictive-like Behavior

Abstract: Ingestion of different nutrients, such as fats and sugars, normally produces different effects on physiology, the brain, and behavior. However, they do share certain neural pathways for reinforcement of behavior, including the mesolimbic dopamine (DA) system. When these nutrients are consumed in the form of binges, this can release excessive DA, which causes compensatory changes that are comparable to the effects of drugs of abuse. In this article, we review data obtained with animal models of fat and sugar bingeing. The concept of "food addiction" is described and reviewed from both clinical and laboratory animal perspectives. Behavioral manifestations of addictive-like behavior and concomitant alterations in DA and opioid systems are compared for sugar and fat bingeing. Finally, in relation to eating disorders and obesity, we discuss how fat may be the macronutrient that results in excess body weight, and sweet taste in the absence of fat may be largely responsible for producing addictive-like behaviors that include a withdrawal syndrome.

Synaptic plasticity and memory: an evaluation of the hypothesis

Abstract: Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the infor- mation storage underlying the type of memory mediated by the brain area in which that plasticity is observed." We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.

Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming

Abstract: The "fetal" or "early" origins of adult disease hypothesis was originally put forward by David Barker and colleagues and stated that environmental factors, particularly nutrition, act in early life to program the risks for adverse health outcomes in adult life. This hypothesis has been supported by a worldwide series of epidemiological studies that have provided evidence for the association between the perturbation of the early nutritional environment and the major risk factors (hypertension, insulin resistance, and obesity) for cardiovascular disease, diabetes, and the metabolic syndrome in adult life. It is also clear from experimental studies that a range of molecular, cellular, metabolic, neuroendocrine, and physiological adaptations to changes in the early nutritional environment result in a permanent alteration of the developmental pattern of cellular proliferation and differentiation in key tissue and organ systems that result in pathological consequences in adult life. This review focuses on those experimental studies that have investigated the critical windows during which perturbations of the intrauterine environment have major effects, the nature of the epigenetic, structural, and functional adaptive responses which result in a permanent programming of cardiovascular and metabolic function, and the role of the interaction between the pre- and postnatal environment in determining final health outcomes.